The addition of abemaciclib to trastuzumab, with or without fulvestrant, provided a numerical overall survival improvement over standard-of-care trastuzumab plus chemotherapy in patients with hormone receptor–positive, HER2-positive advanced breast cancer, according to data from the monarcHER trial.
Fabrice André, MD, PhD
The addition of abemaciclib (Verzenio) to trastuzumab (Herceptin), with or without fulvestrant (Faslodex), provided a numerical overall survival (OS) improvement over standard-of-care trastuzumab plus chemotherapy in patients with hormone receptor–positive, HER2-positive advanced breast cancer, according to findings from a prespecified final analysis of the phase 2 monarcHER trial (NCT02675231).1
Fabrice André, MD, PhD, director of research at Gustave Roussy in Villejuif, France, presented the data at the 2022 ESMO Congress.
As of the data cutoff on March 31, 2022, the median OS in arms A (experimental regimen plus fulvestrant), B (experimental regimen alone), and C (control therapy) were 31.1 months (arms A vs C: HR, 0.71; 95% CI, 0.48-1.05; 2-sided P value = .086), 29.2 months (arms B vs C: HR, 0.84; 95% CI, 0.57-1.23; 2-side P value = .365), and 20.7 months, respectively. In comparing arms A and C, the triplet regimen with the oral CDK4/6 inhibitor induced a statistically significant improvement in OS compared with trastuzumab plus chemotherapy.
Moreover, there was a consistent benefit observed with the pooled abemaciclib arms across all pre-specified subgroups.
An exploratory analysis of RNA sequencing of intrinsic subtypes showed that luminal subtypes of disease compared with non-luminal subtypes were associated with longer median progression-free survival (PFS; 8.6 months vs 5.4 months; HR, 0.54; 95% CI, 0.38-0.79) and OS (31.7 months vs 19.7 months; HR, 0.68; 95% CI, 0.46-1.00).
André said there were no new adverse events (AEs).
In the randomized, multicenter, open-label phase 2 trial, patients were randomized 1:1:1 to receive either abemaciclib plus fulvestrant and trastuzumab (arm A; n = 79), abemaciclib plus trastuzumab (arm B; n = 79), or trastuzumab plus standard-of-care chemotherapy (arm C; n = 79) at doses of:
Investigator-assessed PFS in the intent-to-treat population (arm A vs C, then arm B vs C) served as the primary end point. Secondary end points included OS, overall response rate, patient-reported outcomes, and pharmacokinetics. Safety was also assessed in any patient who received at least 1 dose of study treatment.
Patients were eligible if they were 18 years or older; had hormone receptor–positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease; had an ECOG performance status of 0 or 1; had previously received at least 2 HER2-directed targeted therapies for advanced disease; and has prior ado-trastuzumab emtansine (T-DM1; Kadcyla) and taxane therapy.
In the previously reported data, after a median follow-up of 19.0 months (range, 14.7-25.1), treatment on arm A compared with arm C induced superior median PFS at 8.3 months (95% CI, 5.9-12.6) vs 5.7 months (95% CI, 5.4-7.0) with control therapy for a reduction in the risk for disease progression or death of 33% (HR, 0.67; 95% CI, 0.45-1·00; P = .051).2
The most common grade 3/4 treatment-emergent adverse event (TRAE) in arms A, B, and C, was neutropenia (27% vs 22% vs 26%, respectively). In arm A, the most common serious AEs included pyrexia (4%), diarrhea (3%), urinary tract infection (3%), and acute kidney injury (3%).